The bacterium Bordetella pertussis is the causative agent of pertussis or whooping cough, a serious and potentially fatal infectious disease of the upper respiratory tract. Pertussis vaccines currently used contain chemically inactivated whole cells of B. pertussis. More recently, acellular pertussis vaccines were developed which are based on material obtained by chemical and physical fractionation of B. pertussis cultures.
Whole cell vaccines contain the antigenic components necessary to provide protection from pertussis disease and their efficacy in humans is generally well accepted. However, whole cell vaccines also contain components which are not required for protection. Some of these components, such as endotoxin, have been implicated in undesired effects which may occur coincident with pertussis immunization (Bibliography 1).
Acellular vaccines are less complex than whole cell vaccines, because they lack endotoxin, DNA, and cellular components not associated with protection, such as extraneous enzymes and other proteins. However, acellular vaccines, such as that developed by Takeda Chemical Industries, Ltd., Osaka, Japan (2) and the Kanonji Institute, The Research Foundation for Microbial Diseases (Biken) of Osaka University, Japan (3), may also contain more components than necessary to confer protection. In addition, some acellular vaccines are tedious to produce, because of their requisite co-purification procedure (1).
Based on animal protection studies, several B. pertussis antigens have been proposed as protective antigens, namely, lymphocytosis promoting factor (LPF, also known as pertussis toxin, which is detoxified before use and is thereafter referred to as pertussis toxoid) (1), histamine sensitizing factor, or islet activating factor (4), filamentous hemagglutinin (FHA) (1), agglutinogens such as fimbriae (5), and outer membrane proteins (1), such as the 69 kilodalton (69K) outer membrane protein (6).
Each of these antigens is able to individually protect animals in one or more animal models. However, animal models are of limited use in predicting efficacy of a pertussis vaccine in humans, because the B. pertussis organism is a natural pathogen only in humans (7).
Based on animal data, two acellular vaccines developed by Biken, one containing LPF and FHA, and one containing LPF alone were evaluated in humans (8,9). Overall, the efficacies of these two vaccines were lower than that of whole cell vaccines. The acellular Biken vaccines were only 58-69% (LPF and FHA) or 41-55% (LPF alone) efficacious in conferring protection as compared to the 85-95% efficacy of the whole cell vaccine (8,9). This indicates that other antigens may need to be included to obtain efficacious pertussis vaccines.